A novel, nonsteroidal inhibitor of androgen binding to the rat androgen binding protein: diethyl [[[3-(2,6-dimethyl-4-pyridinyl)-4-fluorophenyl]amino]methylene] propanedioate.
In vitro binding studies demonstrate the binding specificity of a series of 4-aryl-2,6-dimethylpyridines for the rat epididymal androgen binding protein (rABP). The compounds bound competitively to rABP but have very weak or no demonstrable affinity for rat ventral prostate androgen receptor and human sex hormone binding globulin. In particular, compound 11, diethyl [[[3-(2,6-dimethyl-4-pyridinyl)-4-fluorphenyl]amino]methylene] propanedioate, bound with high affinity to rABP (binding affinity about 1/3 that of the endogenous ligand 5 alpha-dihydrotestosterone). However, additional in vitro binding studies indicated that 11 did not bind to testicular or epididymal ABP from rabbit, rhesus monkey, and human. Nevertheless, the specificity and relatively high affinity of these nonsteroidal compounds make them unique and potentially ideal agents for the study of the role of ABP in spermatogenesis and sperm maturation in the rat.
Winneker
R C
RC
Department of Pharmacology, Sterling Research Group, Rensselaer, New York 12144.
Wagner
M M
MM
Singh
B
B
D000727:Androgen-Binding Protein / Q000378:metabolism*; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D013196:Dihydrotestosterone / Q000378:metabolism; D004822:Epididymis / Q000378:metabolism; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D015394:Molecular Structure; D011467:Prostate / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013045:Species Specificity
D000727:Androgen-Binding Protein; D000728:Androgens; D011725:Pyridines; D011944:Receptors, Androgen; D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; C062438:diethyl (((3-(2,6-dimethyl-4-pyridinyl)-4-fluorophenyl)amino)methylene)propanedioate